Lulu Han

Stability of polydopamine and poly(DOPA) melanin-like films on the surface of polymer membranes under strongly acidic and alkaline conditions

This study investigated the stability of polydopamine and poly(3,4-dihydroxyphenylalanine) (poly(DOPA)) melanin-like films on the surface of polymer substrates. Three polymer membranes, polypropylene (PP), poly(vinylidenefluoride) (PVDF) and nylon, were modified with polydopamine or poly(DOPA), and then immersed in 0.1M HCl or NaOH, followed by UV-vis spectrometry analysis to detect the presence of film detachment. The results showed that the outer parts of both polydopamine and poly(DOPA) films were detached, probably due to electrostatic repulsion between the polymers within the film, when the modified membranes were washed in HCl or NaOH solution. These two films were more stable in strongly acidic solution, but the stability of poly(DOPA) film was better than that of polydopamine film. Compared to the films on the surface of PVDF or nylon membrane, films on PP surface showed the lowest stability, possibly because of the hydrophobic property of PP. The process of film detachment was analyzed by GPC, which showed that unreacted dopamine or DOPA monomers were still present in the freshly formed films. The unreacted monomers, as well as polydopamine or poly(DOPA) that were incorporated in the film via noncovalent interactions, became detached when the film was exposed to strongly acidic or alkaline solution. Oxidation of freshly formed films could significantly enhance their stability. The results therefore provide us with a better understanding of the stability of melanin-like films, and allow us to develop an effective strategy for constructing stable films.

Highly flexible heparin-modified chitosan/graphene oxide hybrid hydrogel as a super bilirubin adsorbent with excellent hemocompatibility

As a pathogenic toxin, bilirubin is generally removed from blood by hemoperfusion for the remission of liver disease or to gain time for patients waiting for liver transplantation. However, the development of bilirubin adsorbents with excellent mechanical properties, adsorption performance and hemocompatibility is still a considerable challenge. In this work, a heparin-modified chitosan/graphene oxide hybrid hydrogel (hep-CS/GH) has been developed for bilirubin adsorption using a lyophilization-neutralization-modification strategy. The as-prepared hybrid hydrogel displayed a unique foam-like porous structure and excellent mechanical flexibility. It was revealed that the incorporation of graphene oxide into the chitosan matrix enhanced both the compressive strength and the Youngs modulus of the hybrid hydrogel, as well as its adsorption capacity for bilirubin. The maximum adsorption capacity of hep-CS/GH for bilirubin was 92.59 mg g-1, according to the Langmuir isotherm model. It was demonstrated that hep-CS/GH successfully competed with albumin, and could effectively adsorb bilirubin from a bilirubin-enriched serum. After the hydrogel was modified with heparin, protein adsorption, platelet adhesion and hemolysis were reduced, and the plasma clotting time was prolonged from 4.1 to 23.6 min, indicating the superior hemocompatibility of hep-CS/GH. Therefore, this study may pave the way for improving the performance of the adsorbent in removing blood toxins.

Anticoagulant surface coating using composite polysaccharides with embedded heparin-releasing mesoporous silica

Release of heparin from the surface of biomaterials is a feasible and efficient manner for preventing blood coagulation because of the high bioactivity of free heparin and a low application dosage compared to intravenous injection of heparin. Here we report a novel method featuring a blend of heparin-loaded SBA-15, catechol-modified chitosan (CCS), and heparin as a heparin-releasing film. The release of heparin was based on its leakage from heparin-loaded amino-functionalized mesoporous silica SBA-15 (SBA-15-NH2), which was controlled by the amino density of the SBA-15-NH2. Heparin-loaded SBA-15-NH2, CCS, and heparin were mixed together, and the mixture was cast onto the surface of a polydopamine-modified substrate, forming a heparin-releasing film on the surface of the substrate. The polydopamine acted as an adhesive interlayer that stabilized the film coated on the substrate. The sustained release rates of heparin from the film ranged from 15.8 to 2.1 μg/cm(2)/h within 8 h. The heparin-releasing film showed low fibrinogen adsorption, platelet adhesion, and hemolysis rate, indicating that it has good blood compatibility. This new approach would be very useful for modifying the surface of versatile blood-contacting biomaterials and ultimately improve their anticoagulation performance.

Galloyl groups-regulated fibrinogen conformation: Understanding antiplatelet adhesion on tannic acid coating

Fibrinogen (Fgn) has been identified as the key protein in the process of biomaterial-induced platelet adhesion. We have recently reported a facile and effective method for constructing platelet-repellent surface using a natural polyphenol component tannic acid (TA). However, the mechanism by which the TA surface repels platelets was not fully understood. To address this issue, we investigated the adsorption of Fgn (amount and conformation) on four TA-functionalized surfaces with different amounts of galloyl groups and the potential for platelet adherence on these surfaces. The experimental results indicated that the four TA-functionalized surfaces adsorbed a similar amount of Fgn, but the conformation and bioactivity of the adsorbed Fgn and the subsequent platelet adherence were quite different among the surfaces. The TA surface with the most galloyl groups induced minimal changes in the conformation of Fgn, a result of the α and γ chains of the adsorbed Fgn being highly inactive on the surface, thus leading to an outstanding antiplatelet adhesion performance. With a decreased amount of galloyl groups, the activity of the α chain in the adsorbed Fgn remained unchanged, but the activity of the γ chain and the extent of platelet adhesion gradually increased. This work provided a new concept for controlling platelet adhesion on solid materials, and we envision that the TA film could have potential applications in the development of new blood-contacting biomaterials in the future.nnnSTATEMENT OF SIGNIFICANCEnReducing platelet adhesion on material surfaces is of tremendous scientific interest in the field of blood-contacting biomaterials, but it remains a big challenge due to the highly adhesive nature of the platelets. In this study, we demonstrated for the first time that tannic acid surface with abundant galloyl groups could induce minimal conformational changes of fibrinogen, eventually leading to an outstanding antiplatelet adhesion effect. In addition, the platelet adhesion response could be easily controlled through regulating the amount of galloyl groups on the surface. This work provided a new strategy for controlling platelet adhesion on solid materials, which was totally different from existing methods such as construction of physically patterned surfaces, modification of inert hydrophilic polymers or appending bioactive moieties to target surfaces.

A facile method to oriented immobilization of His-tagged BirA on Co3+-NTA agarose beads

A facile and economical method was established for the oriented immobilization of biotin ligase (BirA) on Co3+-NTA sepharose through H2O2 oxidation of Co2+ and His-tag. His-tag of the BirA were designed at both N-terminal (His-BirA) and C-terminal (BirA-His), respectively. Immobilization of the His-BirA was performed, realized to 92.85% using by 10u2009mM H2O2 without compromising catalytic activity. Because amounts of ions on matrix were far more than that of the immobilized BirA, EDTA should be used to remove residual ions before catalyzing, while it should be limited to lower than 30u2009mM, and imidazole ranging from 50 to 250u2009mM could be added in the catalytic system. When 10u2009mM EDTA and 50u2009mM imidazole were used, over 90% of substrates were obtained from the matrix. Moreover, the His-BirA showed higher immobilization rate than the BirA-His, while both of them appeared high catalytic abilities at pH ranging from 6.5 to 9.0, indicating versatile options in the biotinylation of proteins with different pH stabilities. Under the best catalytic conditions, the both immobilized His-BirA and BirA-His exhibited the same activity as the free. When the enzyme was incubated at different pH (pH 3.0, 4.0, 5.0, 10.0 and 11.0) and temperature (40u2009°C, 50u2009°C and 60u2009°C), the immobilized His-BirA showed less pH-sensitive, overall preferable thermo-stability than the free, making it a more desirable option for storage and transportation. More importantly, the reusability of the immobilized His-BirA implied a promising value in industrialization.

Removal of indoxyl sulfate by water-soluble poly-cyclodextrins in dialysis

Indoxyl sulfate (IS) is a uremic toxin related to the progression of chronic kidney diseases. Removal of IS from the plasma would reduce the risk of cardiovascular disease. In this study, crosslinked poly-β-cyclodextrins (PCDs) were used as a water-soluble adsorbent agent for IS in dialysis for the first time. The molecular weight of PCDs was found to be proportional to the crosslinking time between β-cyclodextrin monomers and epichlorohydrin, yet the proportion of β-cyclodextrin that reacted with epichlorohydrin decreased. It was observed that PCD after 2u202fh crosslinking yielded the best IS-binding capability in PBS, while reaching the binding equilibrium within 30u202fmin and yielding a maximum binding capability of 45u202fmgu202fg-1. Furthermore, the binding mechanism was investigated by two-dimensional nuclear magnetic resonance, Jobs plot method, and salt treatments. To simulate the clinical removal of IS we established a macro-dialysis and added PCD obtained from 2u202fh crosslinking (PCD1) to the dialysate. The removal of plasma IS from the dialysate by PCD1 was about twice as much as that removed from the dialysate without PCD1. Therefore, crosslinked poly-β-cyclodextrins may represent a simple, low-cost, and effective IS removal strategy with great potential for removing other hydrophobic plasma-bound toxins in dialysis. It could also serve as a supplement for the existing non-adsorbent added therapy.